Melatonin (N-acetyl-5-methoxytryptamine), which is a hormone synthesized and secreted principally in the pineal gland, increases in dark circumstances and decreases in light circumstances. Further, melatonin exerts suppressively on pigment cells or female gonad and acts as a synchronous factor of biological clock while taking part in transmittance of photoperiodic code. Therefore, melatonin is considered to be possibly used for the therapy of diseases related with melatonin activity, such as reproduction and endocrinic disorders, sleep-awake rythm disorders, jet lag syndrome and various disorders related to ageing. Recently it was reported in Ann. N.Y. Acad. Sci., Vol. 719, PP.456-460 (1994) that the production of melatonin decline steadily into old age and the supplementing melatonin could reset the body's aging clock; However, in "Bioorganic & Medicinal Chemistry Letters, Vol.4, p.1485 (1994)", there is described that, when the action on central nervous system is expected, melatonin is shown to be inactive by a peripheral administration.
As a compound having a melatonin receptor affinity,
1) a compound having acylamino group at the 2-position of tetrahydronaphthalene and of the formula ##STR2## PA0 2) a compound having acylaminoethyl group at the 1-position of naphthalene and of the formula ##STR3## PA0 3) (naphthylethyl)ureas are described in EP-A-530087. PA0 1) a compound of the formula ##STR4## PA0 2) a compound of the formula ##STR5## PA0 3) a compound of the formula ##STR6## PA0 4) a compound of the formula ##STR7## PA0 (1) the compound (I) or salts thereof, PA0 (2) the compound described in the above (1), in which R.sup.1 and R.sup.2 are independently a hydrogen atom or an optionally substituted hydrocarbon group, or R.sup.1 and R.sup.2, taken together with the adjacent carbon atom, may form a spiro ring, R.sup.3 represents an optionally substituted hydrocarbon group, an optionally substituted amino group or a substituted hydroxyl group, PA0 (3) the compound described in the above (1), in which the hydrocarbon group is a C.sub.1-6 aliphatic hydrocarbon group, a C.sub.3-6 monocyclic saturated hydrocarbon group or a C.sub.6-10 aromatic hydrocarbon group, PA0 (4) the compound described in the above (1), in which the heterocyclic group is a 5- to 7-membered heterocyclic group having 1 to 3 hetero-atoms selected from nitrogen, oxygen and sulfur, PA0 (5) the compound described in the above (1), in which the spiro ring is a 3 to 8-membered ring, PA0 (6) the compound described in the above (1), in which the substituent of the amino group is an optionally substituted lower alkyl group or an optionally substituted aryl group, PA0 (7) the compound described in the above (1), in which the substituted hydroxyl group is an optionally substituted lower alkoxy group, PA0 (8) the compound described in the above (1), in which R.sup.1 and R.sup.2 are independently a hydrogen atom, a lower alkyl group or an aryl group, PA0 (9) the compound described in the above (1), in which R.sup.1 and R.sup.2 are independently a hydrogen atom or a lower alkyl group, PA0 (10) the compound described in the above (1), in which R.sup.3 is (i) an optionally substituted lower alkyl group, (ii) an optionally substituted lower cycloalkyl group, (iii) an optionally substituted lower alkenyl group, (iv) an optionally substituted aryl group, (v) an optionally substituted lower alkylamino group, (vi) an optionally substituted arylamino group, (vii) an optionally substituted 5- or 6-membered nitrogen-containing heterocyclic group or (viii) an optionally substituted lower alkoxy group, PA0 (11) the compound described in the above (1), in which R.sup.3 is an optionally halogenated C.sub.1-3 alkyl group, PA0 (12) the compound described in the above (1), in which R.sup.4 is a hydrogen atom, PA0 (13) the compound described in the above (1), in which ......... is a single bond, PA0 (14) the compound described in the above (1), in which n is an integer of 1 to 3, PA0 (15) the compound described in the above (1), in which n is 1, PA0 (16) the compound described in the above (1), in which m is 1 or 2, PA0 (17) the compound described in the above (1), in which the ring A is a benzene ring having 1 to 3 substituents selected from the group consisting of (i) a halogen atom, (ii) a lower alkyl group, (iii) a lower alkoxy group optionally substituted with an aryl group, (iv) hydroxyl group and (v) a mono-lower alkylamino group, PA0 (18) the compound described in the above (1), in which the ring A is represented by the formula ##STR11## PA0 (19) the compound described in the above (1), in which m is 1, n is 2 and ......... is a single bond, PA0 (20) the compound described in the above (1), in which m is 1, n is 2 and ......... is a double bond, PA0 (21) the compound described in the above (1), in which m is 1 or 2, n is 1 and ......... is a single bond, PA0 (22) the compound described in the above (1), in which m is 1, n is 3 and ......... is a double bond, PA0 (23) the compound described in the above (1), in which R.sup.1, R.sup.2 and R.sup.4 all are a hydrogen atoms, PA0 (24) the compound described in the above (23), in which R.sup.3 is an optionally halogenated lower alkyl group, PA0 (25) the compound described in the above (23), in which R.sup.3 is a lower cycloalkyl group, PA0 (26) the compound described in the above (18), in which R.sup.1, R.sup.2 and R.sup.4 all are a hydrogen atoms, R.sup.3 is an optionally halogenated lower alkyl group and both of m and n are 1, PA0 (27) the compound described in the above (1), which is the compound represented by the formula: ##STR12## PA0 (28) the compound described in the above (1), which is (S)-1-[2-(acetylamino)ethyl]-6-methoxyindan, (S)-6-methoxy-1-[2-(trifluoroacetylamino)ethyl]indan, (S)-1-[2-(cyclopropylcarbonylamino)ethyl]-6-methoxyindan, (S)-1-[2-(propionylamino)ethyl]-6-methoxyindan, (S)-1-[2-(isobutyrylamino)ethyl]-6-methoxyindan, (S)-1-[2-(acetylamino)ethyl]-7-methoxy-1,2,3,4-tetrahydronaphthalene, (S)-7-methoxy-1-[2-(trifluoroacetylamino)ethyl]-1,2,3,4-tetrahydronaphthal ene or (S)-1-[2-(cyclopropylcarbonylamino)ethyl]-7-methoxy-1,2,3,4-tetrahydronaph thalene, PA0 (29) the compound described in the above (1), which is (S)-1-[2-(trifluoroacetylamino)ethyl]-6-methoxyindan, PA0 (30) the compound described in the above (1), which is (S)-1-[2-(propionylamino)ethyl]-6-methoxyindan, PA0 (31) (S)-1-(2-aminoethyl)-6-methoxyindan or a salt thereof, PA0 (32) a process for producing a compound described in the above (1), which comprises reacting a compound represented by the formula: ##STR13## PA0 (33) a pharmaceutical composition which comprises a compound described in the above (1), if necessary together with a pharmaceutically acceptable carrier, PA0 (34) the composition described in the above (33), which has a binding affinity for melatonin receptor, PA0 (35) the composition described in the above (34), which is a regulating agent of circadian rhythm, PA0 (36) the composition described in the above (35), which is a regulating agent of sleep-awake rhythm, PA0 (37) the composition described in the above (36), which is a regulating agent of time zone change syndrome, PA0 (38) the composition described in the above (35), which is a therapeutic agent of sleep disorders, PA0 (39) a composition having a binding affinity for melatonin receptor which comprises a compound (Ia) or a salt and a pharmaceutically acceptable carrier, and PA0 (40) the composition described in the above (39), which is a melatonin receptor agonistic composition.
wherein R.sub.1 and R.sub.2 are independently, H, alkoxy etc., R.sub.3 and R.sub.5 are H etc., R.sub.4 is aryl, C.sub.1-4 alkyl etc., is described in EP-A-420064,
wherein R is propyl, butyl, cyclopropyl etc., is described in "Journal of Medicinal Chemistry, No.35, pp.1484-1486, (1992)" and
And, as compounds having a benzocycloalkene structure
wherein R, R.sub.1 and R.sub.2 are independently H, lower alkoxy etc., R.sub.3 and R.sub.4 are independently H, lower acyl (--CO--R.sup.5) etc., R.sup.5 is lower alkyl, n is 1 to 4, and having adrenaline activity and being useful as therapeutic agents in the treatment of hypertension is described in GB 2093837,
wherein R.sub.1, R.sub.2 R.sub.3 and R.sub.4 are independently H, lower alkyl, and having .alpha..sub.2 -adrenergic receptor agonist activity and being useful for hypertension is described in CA 1221639,
which is used as an intermediate of eptazocin hydrobromide being useful as a narcotic-antagonizing analgesic for relieving post-operative pains is described in EP-A-384917,
which is used as a starting material of tetralin having dopamine activity is described in "Journal of Medicinal chemistry, No. 26, p. 813, (1983)".
None of them refers to the melatonin receptors affinities.
A melatonin agonist, which is different from melatonin in the structure, has stronger activities than those of melatonin, is metabolicaly stable and is excellent in the transferability into brain, can be expected to show superior therapeutic effects to those of melatonin. And, when the antagonistic activities of melatonin are desired, creation of a new melatonin antagonist is necessary.
At the present circumstances, no compounds which are fully satisfactory in the activities of melatonin receptors, in metabolical stability and in transferability into brain have been found. So, development of compounds, which are different from the above-mentioned known compounds in chemical structure, have excellent melatonin receptor affinities and are fully satisfactory as medicines, is ardently desired.